Bone Morphogenetic Protein Family
Bone morphogenetic proteins: from basic science to clinical applications.
J Bone Joint Surg Am. 2001;83-A Suppl 1(Pt 1):S1-6. Review
The role of bone morphogenetic proteins (BMPs) in bone formation during development and in fracture-healing is now well established. In experimental animals, BMPs elicit bone formation in ectopic sites and healing of critical-sized segmental bone defects. Many of the studies on the capacity of BMPs to elicit the healing of segmental bone defects have been carried out in orthopaedic research laboratories and are familiar to orthopaedic surgeons.
However, until recently little was known about the cellular and molecular mechanisms by which BMPs elicit bone formation. In a series of stunning studies over the last several years, molecular cell biologists working intensively in several laboratories have elucidated some of these mechanisms. When BMPs bind to their cell surface receptors on mesenchymal cell, a BMP signaling cascade is activated. Signals are sent via specific proteins to the cell nucleus. This results in the expression of genes that lead to the synthesis of macromolecules involved in cartilage and bone formation, and the mesenchymal cell becomes a chondrocyte or an osteoblast.
The development of knowledge in this area of BMP signal transduction during the last several years has been phenomenal and has provided a substantial amount of new information that is clear-cut, specific, and useful. Some of this new information may be of clinical relevance because it suggests potential therapeutic approaches to enhance or suppress new bone formation. Several of the studies on the mechanisms of BMP signal transduction presented at the International Conference on Bone Morphogenetic Proteins (held in Lake Tahoe, California, June 7 through 11, 2000) have been included in this supplement. In each article, the authors have included in the introductory section a lucid summary of the development of knowledge in a particular area.
Interleukin-17 family and IL-17 receptors.
Cytokine Growth Factor Rev. 2003 Apr;14(2):155-74. PMID: 12651226 Review
Interleukin-17 (IL-17) is a pro-inflammatory cytokine secreted by activated T-cells. Recently discovered related molecules are forming a family of cytokines, the IL-17 family. The prototype member of the family has been designated IL-17A. Due to recent advances in the human genome sequencing and proteomics five additional members have been identified and cloned: IL-17B, IL-17C, IL-17D, IL-17E and IL-17F. The cognate receptors for the IL-17 family identified thus far are: IL-17R, IL-17RH1, IL-17RL (receptor like), IL-17RD and IL-17RE. However, the ligand specificities of many of these receptors have not been established. The IL-17 signaling system is operative in disparate tissues such as articular cartilage, bone, meniscus, brain, hematopoietic tissue, kidney, lung, skin and intestine. Thus, the evolving IL-17 family of ligands and receptors may play an important role in the homeostasis of tissues in health and disease beyond the immune system. This survey reviews the biological actions of IL-17 signaling in cancers, musculoskeletal tissues, the immune system and other tissues.